Anticipatory goal-directed processes, such as attention and motivation, have a significant impact on learning and memory, yet much is still unknown about how such processes exert their influence in the human brain. Episodic memory-memory for specific events-critically relies on the integrity of the structures of the medial temporal lobe (MTL), including the hippocampus (CA fields, dentate gyrus, and subiculum) and parahippocampal gyrus (entorhinal, perirhinal and parahippocampal cortices). The MTL receives direct projections from brain regions involved in attention and reward-based motivation, including posterior parietal cortex (PPC), prefrontal cortex (PFC), and midbrain. Activation of these motivational and attentional networks prior to stimulus presentation may influence memory formation by facilitating stimulus processing within the MTL. The research presented in this proposal will use functional magnetic resonance imaging (fMRI) to examine how goal-directed processes initiated prior to stimulus presentation recruit attentional and motivational brain networks and influence memory formation in the MTL. Experiment 1 will use high-resolution fMRI to test the hypothesis that reward-based motivation differentially affects MTL subregional function through interactions with midbrain structures. We will examine whether motivational incentives that elicit activation from dopaminergic midbrain prior to stimulus presentation enhance memory encoding within MTL subregions. Experiment 2 will test the hypothesis that attentional cues can bias MTL processing and facilitate memory formation. We will examine if anticipatory cues that indicate task-relevant goals elicit activation from PPC, PFC, and task-relevant MTL subregions prior to stimulus presentation, and whether this results in enhanced episodic encoding. Experiment 3 will examine the effects of reward-based motivation on associative memory formation under conditions of full and divided attention to test the hypothesis that motivation drives MTL-based memory formation through allocation of attentional resources. By increasing understanding of memory function within the MTL, this work has the ability to shed light on changes in MTL structure and function known to occur in normal aging and mental illnesses, including Alzheimer's disease, depression, bipolar disorder and schizophrenia. The proposed research examines how interactions between dopaminergic midbrain and MTL influence memory, which will provide insight into disorders that involve disruptions of the DA system, including Parkinson's disease, depression, bipolar disorder, and schizophrenia. This work may prove particularly informative for understanding the MTL dysfunction and impairments in memory and attention that occur in schizophrenia. PUBLIC HEALTH RELEVANCE: The proposed research examines how motivation and attention influence memory formation in the human brain. This work has the ability to increase understanding of changes in brain function known to occur in normal aging and mental illnesses, including Alzheimer's Disease, depression, bipolar disorder and schizophrenia.